PROJECT SUMMARY The ability of public safety personnel to identify cannabis impaired driving has lagged behind the dramatic shifts in legal access to cannabis in the U.S. and other countries. Reducing the risk related to cannabis impaired driving will depend on accurate methods to detect impairment and evidence-informed guidance on how dose, route of administration, and temporal factors are associated with impairment. We will leverage our operational driving simulator laboratory to test innovative devices for accuracy and predictive value in identifying impairment from cannabis use. We will test portable devices that measure psychomotor performance (on a tablet) and oculomotor performance (in a goggle-based instrument). Using an efficient, within-subjects design, performance on these devices will be compared to driving simulator measures obtained before and after self-administered cannabis by occasional and daily cannabis users. We will also examine the pharmacokinetic profile of THC (tetrahydrocannabinol) and its metabolites in relation to pharmacodynamic measurements of psychomotor function. We will conduct 3 phases of research over 5 years. In phase 1 we will collect standard venous and innovative (100 L) capillary blood samples before and after cannabis use among a cohort of cannabis users with varied cannabis use histories (n=30) to examine the pharmacokinetic profile of blood cannabinoids over time. In Phase 2, we will recruit a cohort of cannabis users to complete assessments before and after smoking cannabis to examine the predictive value of established psychomotor tests, ocular tests, and blood cannabinoid profiles against validated benchmarks of driving simulator performance. A subgroup of non-using control subjects will be enrolled to adjust for learning effects (total n=120). In Phase 3 we will use a similar approach to test the effect of edible cannabis products on impairment (n=90). These innovative technologies are highly portable and have the promise to offer an objective assessment of impairment due to cannabis and other psychoactive drugs at or near the roadside or at the workplace. Successful completion of our study will provide public health and safety officials, medical and recreational cannabis users, health care providers, employers and the judicial system with novel information regarding cannabis use and driving safety.